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Rose McGowan made her film debut in a brief role in the comedy Encino Man (1992), McGowan achieved wider recognition for her performance in the dark comedy The Doom Generation (1995), receiving an Independent Spirit Award nomination for Best Debut Performance. She had her breakthrough in the horror film Scream (1996) and subsequently headlined the films Going All the Way (1997), Devil in the Flesh (1998) and Jawbreaker (1999).

During the 2000s, McGowan became known to television audiences for her role as Paige Matthews in The WB supernatural drama series Charmed (2001–2006). She went on to star in Robert Rodriguez and Quentin Tarantino's double-feature film Grindhouse (2007), for which she was nominated for the Saturn Award for Best Actress and the Scream Award for Best Scream Queen. She played the role of Josie Acosta in the action-thriller series Chosen (2014).

In 2017, Time recognized McGowan as one of the Silence Breakers, the magazine's Person of the Year, for speaking out about sexual assault and harassment, specifically in regard to the Harvey Weinstein sexual abuse cases and the Me Too movement. She has released a memoir, Brave, and starred in the four-part documentary series Citizen Rose, both in 2018.